Exploring the immune landscape and drug prediction of an M2 tumor‐associated macrophage‐related gene signature in EGFR‐negative lung adenocarcinoma

• Published in: Thoracic cancer Vol. 15; no. 21; pp. 1626 - 1637
• Main Authors: Huang, Yajie, Zhang, Yaozhong, Duan, Xiaoyang, Hou, Ran, Wang, Qi, Shi, Jian
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01.07.2024; John Wiley & Sons, Inc; Wiley
• Subjects: Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - immunology; Adenocarcinoma of Lung - pathology; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; bulk RNA‐seq; Cancer; EGFR‐negative lung adenocarcinoma; ErbB Receptors - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; immune landscape; Immunotherapy; Kruppel-Like Factor 4; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lymphocytes; Male; Medical prognosis; Melanoma; Mitochondria; Mortality; Mutation; Original; Prognosis; single‐cell RNA‐seq; Survival analysis; Tumor Microenvironment - immunology; Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism; tumor‐associated macrophage; single‐cell RNA‐seq; tumor‐associated macrophage; EGFR‐negative lung adenocarcinoma; bulk RNA‐seq; immune landscape
• ISSN: 1759-7706; 1759-7714; 1759-7714
• DOI: 10.1111/1759-7714.15375

Background Improving immunotherapy efficacy for EGFR‐negative lung adenocarcinoma (LUAD) patients remains a critical challenge, and the therapeutic effect of immunotherapy is largely determined by the tumor microenvironment (TME). Tumor‐associated macrophages (TAMs) are the top‐ranked immune infiltrating cells in the TME, and M2‐TAMs exert potent roles in tumor promotion and chemotherapy resistance. An M2‐TAM‐based prognostic signature was constructed by integrative analysis of single‐cell RNA‐seq (scRNA‐seq) and bulk RNA‐seq data to reveal the immune landscape and select drugs in EGFR‐negative LUAD. Methods M2‐TAM‐based biomarkers were obtained from the intersection of bulk RNA‐seq data and scRNA‐seq data. After consensus clustering of EGFR‐negative LUAD into different clusters based on M2‐TAM‐based genes, we compared the prognosis, clinical features, estimate scores, immune infiltration, and checkpoint genes among the clusters. Next, we combined univariate Cox and LASSO regression analyses to establish an M2‐TAM‐based prognostic signature. Results CCL20, HLA‐DMA, HLA‐DRB5, KLF4, and TMSB4X were verified as prognostic M2‐like TAM‐related genes by univariate Cox and LASSO regression analyses. IPS and TMB analyses revealed that the high‐risk group responded better to common immunotherapy. Conclusion The study shows the potential of the M2‐like TAM‐related gene signature in EGFR‐negative LUAD, explores the immune landscape based on M2‐like TAM‐related genes, and predict immunotherapy response of patients with EGFR‐negative LUAD, providing a new insight for individualized treatment. The process of M2 Tumor‐Associated Macrophage‐Related Gene Signature Construction.